Crystal structure of the gephyrin-related molybdenum cofactor biosynthesisprotein MogA from Escherichia coli

Molybdenum cofactor (Moco) biosynthesis is an evolutionarily conserved path way in archaea, eubacteria, and eukaryotes, including humans. Genetic defic iencies of enzymes involved in this biosynthetic pathway trigger an autosom al recessive disease with severe neurological symptoms, which usually leads to death in early childhood. The MogA protein exhibits affinity for molybd opterin, the organic component of Moco, and has been proposed to act as a m olybdochelatase incorporating molybdenum into Moco, MogA is related to the protein gephyrin, which, in addition to its role in Moco biosynthesis, is a lso responsible for anchoring glycinergic receptors to the cytoskeleton at inhibitory synapses. The high resolution crystal structure of the Escherich ia coli MogA protein has been determined, and it reveals a trimeric arrange ment in which each monomer contains a central, mostly parallel beta-sheet s urrounded by cu-helices on either side. Based on structural and biochemical data, a putative active site was identified, including two residues that a re essential for the catalytic mechanism.